NASA's future human space exploration strategy includes single and multi-launch missions to various destinations including cis-lunar space, near Earth objects such as asteroids, and ultimately Mars. Each campaign is being defined by Design Reference Missions (DRMs). Many of these missions are complex, requiring multiple launches and assembly of vehicles in orbit. Certain missions also have constrained departure windows to the destination. These factors raise concerns regarding the reliability of launching and assembling all required elements in time to support planned departure. This paper describes an integrated methodology for analyzing launch and assembly reliability in any single DRM or set of DRMs starting with flight hardware manufacturing and ending with final departure to the destination. A discrete event simulation is built for each DRM that includes the pertinent risk factors including, but not limited to: manufacturing completion; ground transportation; ground processing; launch countdown; ascent; rendezvous and docking, assembly, and orbital operations leading up to trans-destination-injection. Each reliability factor can be selectively activated or deactivated so that the most critical risk factors can be identified. This enables NASA to prioritize mitigation actions so as to improve mission success.